Darolutamide Impacts HRQoL Deterioration-Free Survival in nmCRPC

Darolutamide Impacts HRQoL Deterioration-Free Survival in nmCRPC

By Dibash Kumar Das, PhD

In new research presented at the ESMO 2023 Congress, the ARAMIS trial has revealed the remarkable effects of darolutamide (DARO) in preserving health-related quality of life (HRQoL) deterioration-free survival (DetFS) based on prostate-specific antigen (PSA) decline (Abstract 1781P).

ARAMIS (NCT02200614) previously unveiled that darolutamide, when combined with androgen deprivation therapy (ADT), significantly extended metastasis-free survival and lowered the risk of death by 31 percent in nmCRPC patients. Moreover, darolutamide was found to have a positive influence on local disease recurrence and symptom control while delaying HRQoL deterioration. Now, researchers present the profound impact of darolutamide on HRQoL DetFS in ARAMIS, particularly concerning PSA decline.

Patients with nmCRPC were randomized in a 2:1 ratio to receive darolutamide or a placebo, both alongside ADT. Darolutamide-treated patients were further categorized based on their PSA decline from baseline at Week 16 into three groups: PSA decline of ≥90 percent (PSA90), ≥50 percent to <90 percent (PSA50-90), and <50 percent (PSA50). The primary endpoint, DetFS, was defined as the time from randomization until the earliest event of deterioration in HRQoL, which included urinary and bowel symptoms subscales and Functional Assessment of Cancer Therapy-Prostate (FACT-P) prostate cancer subscale (PCS) and Total scores, metastasis, death, or treatment discontinuation. Median DetFS was calculated using Kaplan-Meier estimates.

The findings revealed that among the 955 patients receiving darolutamide, 44.8 percent (403 patients) attained a PSA decline of ≥90 percent (PSA90). “Patients receiving darolutamide who achieved PSA90 4 months after showed longer deterioration-free survival when measuring the EORTC QLQ-PR25 urinary (HR: 0.49 [0.36-0.69]) and bowel (HR: 0.50 [0.36-0.69]) symptoms, and also had longer deterioration-free survival on the FACT-P PCS (HR: 0.60 [0.43-0.83]) and Total Scores (HR: 0.47 [0.32-0.70] compared with those with PSA <50,” highlighted study author Alicia Morgans, MD, MPH, Genitourinary Medical Oncologist and Medical Director of the Survivorship Program at Dana-Farber Cancer Institute.

Moreover, for urinary symptoms, those in the PSA90 group demonstrated a median DetFS of 22.3 months, compared to 18.5 months in the PSA50-90 group and 11.6 months in the <50 percent PSA decline group. Similar trends were observed in bowel symptoms, with the PSA90 group leading in DetFS at 25.6 months, while the PSA50-90 group and the <50 percent PSA decline group showed shorter times, at 14.7 and 11.5 months, respectively.

Additionally, the study showed that patients achieving PSA90 experienced impressive 3-year DetFS rates of 38.0 percent for urinary symptoms and 33.8 percent for bowel symptoms, compared to 31.2 percent and 17.4 percent in the PSA50-90 group and 14.6 percent and 13.3 percent in the <50 percent PSA decline group.

Regarding the clinical significance of HRQoL DetFS and its potential impact on treatment decisions and patient outcomes in nmCRPC, Morgans, in her discussion with Oncology Times, concluded that “HRQoL DetFS serves as a comprehensive composite endpoint over time. It encompasses the duration from randomization to the earliest occurrence of a decline in HRQoL, metastasis, mortality, or treatment discontinuation. The ARAMIS study findings demonstrate that a substantial proportion of nmCRPC patients who received darolutamide achieved PSA90, affirming the favorable cancer control and HRQoL advantages associated with early darolutamide treatment.”

Dibash Kumar Das is a contributing writer.